Cancer remains a major health problem and financial burden on the medical system. While conventional radiologic studies provide an important roadmap for pathologic diagnosis and staging, they often represent the limiting step in our ability for early and accurate detection of disease. If there is to be a significant impact on cancer, there is a need to pursue new strategies to include and utilize a growing knowledge of tumor genetics, molecular biology, and biochemistry in an effort to design new tumor specific imaging agents. Development of a noninvasive imaging study capable of early detection and accurate staging has overwhelming clinical and economic implications. Nuclear medicine studies (SPECT of PET) with tumor specific agents have the potential to be orders of magnitude more accurate then other non-invasive studies, including serum markers and conventional imaging techniques. These studies can provide metabolic, biochemical, physiologic, and anatomic information. Current imaging agents, however, are not uniformly specific or sensitive, and thus this project will continue development of novel small molecules in an effort to design a radiolabeled ligand for cancer imaging. While these efforts specifically focus on a mutant tumor receptor system as a model, the proposed approach for ligand discovery with combinatorial chemistry libraries is applicable to other tumors as well. This type of translational research is absolutely essential if improved outcomes of this devastating disease are to be realized.